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PLoS Pathog. 2008 Feb 8;4(2):e28. doi: 10.1371/journal.ppat.0040028.

Methamphetamine inhibits antigen processing, presentation, and phagocytosis.

Author information

1
Department of Neurology, Columbia University, New York, New York, United States of America.

Erratum in

  • PLoS Pathog. 2008 Mar;4(3). doi: 10.1371/annotation/bd02ad26-a081-4c61-88c2-ebda285b8bca. Nosanchuk, Josh [corrected to Nosanchuk, Joshua D].

Abstract

Methamphetamine (Meth) is abused by over 35 million people worldwide. Chronic Meth abuse may be particularly devastating in individuals who engage in unprotected sex with multiple partners because it is associated with a 2-fold higher risk for obtaining HIV and associated secondary infections. We report the first specific evidence that Meth at pharmacological concentrations exerts a direct immunosuppressive effect on dendritic cells and macrophages. As a weak base, Meth collapses the pH gradient across acidic organelles, including lysosomes and associated autophagic organelles. This in turn inhibits receptor-mediated phagocytosis of antibody-coated particles, MHC class II antigen processing by the endosomal-lysosomal pathway, and antigen presentation to splenic T cells by dendritic cells. More importantly Meth facilitates intracellular replication and inhibits intracellular killing of Candida albicans and Cryptococcus neoformans, two major AIDS-related pathogens. Meth exerts previously unreported direct immunosuppressive effects that contribute to increased risk of infection and exacerbate AIDS pathology.

PMID:
18282092
PMCID:
PMC2242831
DOI:
10.1371/journal.ppat.0040028
[Indexed for MEDLINE]
Free PMC Article

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